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25
JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY December 2017 • Volume 10 • Number 12
O R I G I N A L R E S E A R C H
decreased, approaching baseline scores by
approximately Week 4.
It is always important that proper patient
education is provided regarding expected
skin reactions and their management when
treating patients with AK—particularly those
without prior experience of topical treatment.
Approximately 80 to 90 percent of patients on
topical therapy will experience LSRs such as
erythema, dryness, burning, and pruritus.
18
Thus, providing clear information (including
photographs to support communication) can
help to alleviate fear, and patients can also be
provided with techniques to use at home to help
reduce any pain or itching.
Less than 5 percent of patients in each
treatment group had severe AEs. Treatment-
related AEs were reported in 50.8, 69.8, and
66.1 percent of patients in the face/chest, scalp,
and trunk/extremities groups, respectively;
approximately half of the patients had
application site pain and approximately one-
third had application site pruritus. Based upon
these findings, the safety of the dosing regimen
with once-daily dosing for three consecutive
days was in line with previous dose finding
trials evaluating ingenol disoxate two-day
regimens.
13,14
Efficacy. The three-day treatment regimen
evaluated in this trial demonstrated clinically
relevant efficacy. This was demonstrated both
by the high percentage reduction in AK lesion
count from baseline and also the percentage
of patients who achieved complete clearance
(AKCLEAR 100) by the end of the trial at Week
8. It should also be noted that approximately
two-thirds of patients in the face/chest and
scalp groups and half of the patients in the
trunk/extremities group achieved partial
clearance (AKCLEAR 75) by Week 8. Comparable
levels were observed for reduction in AK lesion
count, as well as partial and complete clearance
at Week 4, indicating that the majority of the
effect on AK lesions was already achieved by this
time point.
Similar findings have been reported
using ingenol disoxate daily dosing for two
consecutive days. Weiss et al
13
observed a
72.7-percent reduction in AK lesion count from
baseline to Week 8 when ingenol disoxate
was administered at 0.037% on the scalp;
the majority of this effect was reached by
Week 4. Similarly, Bourcier et al
14
reported a
79.0-percent reduction in AK lesion count from
baseline at Week 8 when ingenol disoxate
0.018% gel was administered on the face/chest.
Weiss et al
13
reported that when patients
were treated with ingenol disoxate 0.037% gel
on the scalp, 21.9 percent of patients achieved
complete clearance, while 54.7 percent achieved
partial clearance at Week 8. In the Bourcier et
al trial,
14
when treated with ingenol disoxate
0.018% gel on the face/chest, 24.2 percent of
patients achieved complete clearance and 62.9
percent achieved partial clearance at Week 8.
The rate of complete and partial clearance, at
the same concentrations of ingenol disoxate
as used in previous trials, was increased in
the present trial, which is likely due to the
additional treatment day.
The efficacy of ingenol disoxate in
hyperkeratotic/hypertrophic lesions was also
demonstrated by a percentage reduction in AK
lesion count, although this was slightly less
than that observed in the nonhyperkeratotic/
hypertrophic AK lesions. However, due to the
small number of patients with this subtype of
AK lesions and also the low number of lesions
per patient, the CIs for the estimated mean
percent reduction were wide. Approximately
half of patients in the face/chest and scalp
groups and a quarter of patients in the trunk/
extremities group demonstrated complete
clearance of hyperkeratotic/hypertrophic
lesions. These data suggest that ingenol
disoxate might be effective on these lesions,
which are notoriously difficult to treat.
It is important to note that a field therapy
that is highly effective at eliminating clinically
visible lesions, as demonstrated in the reduction
of AK lesion count and clearance rates, is also
likely to eliminate subclinical lesions that are
not visible.
19
Treatment regimen and dose
concentration. This trial evaluated the safety
and efficacy of ingenol disoxate gel at different
concentrations on different anatomical locations
when applied once daily for three consecutive
days. The same treatment regimen (once daily
for three consecutive days) has proved effective
with ingenol mebutate when 0.015% of such
was applied to the face or scalp (25cm
2
).
10
Although complete clearance was slightly lower
in the present trial, it is important to note that
the treatment area was up to 10 times larger
with a greater number of baseline AK lesions,
making complete clearance more difficult to
achieve. A more appropriate comparison for
trials in which treatment area sizes are different
is percentage reduction in AK lesion count; in
FIGURE 7. Percentage of patients with AKCLEAR 75 at Weeks 4 and 8; excludes hyperkeratotic/hypertrophic lesions
AKCLEAR 75: partial clearance of actinic keratoses defined as 75 percent reduction or more in baseline AK lesion count